Haemostasis and Anti-coagulant Drugs

Haemostasis and Anti-thrombotic Drugs

• Haemostasis is the process that stops bleeding by keeping blood within a damaged blood vessel, with three phases: vascular, platelet, and coagulation.

Classification of Anti-thrombotic Drugs

• Anti-thrombotic drugs interfere with the haemostatic system and are divided into three groups: anti-coagulant drugs, anti-platelet drugs, and fibrinolytics.

Classification of Anti-coagulant Drugs

• Anti-coagulant drugs are divided into:
  • Heparin and related drugs (heparin, low molecular weight heparins, fondaparinux)
  • Vit K antagonists (warfarin, acenocoumarol)
  • Direct thrombin (factor IIa) inhibitors (hirudin, bivalirudin, dabigatran)
  • Direct factor Xa inhibitors (rivaroxaban, apixaban, edoxaban)

Heparin and Related Drugs

• Mechanism of action: bind to anti-thrombin III, activating it to inhibit factor Xa and thrombin
• Pharmacodynamics: used in treatment of DVT and pulmonary embolism, unstable angina, or acute MI
• Pharmacokinetics: IV/SC administration, rapid onset, low protein binding, doesn't cross placental barrier
• Side effects: bleeding, thrombocytopenia, autoimmune antibodies against platelets, alopecia, osteoporosis (long-term use)
• Lab control of treatment: APTT (1.5 - 2.5)
• Antidote: i.v protamine sulphate

Vit K Antagonists (Warfarin, Acenocoumarol)

• Mechanism of action: prevent liver synthesis of Vit K-dependent clotting factors and inhibit endogenous anti-coagulants
• Pharmacodynamics: prevent progression/recurrence of acute DVT/pulmonary embolism, venous thromboembolism during orthopaedic surgery, MI in patients with unstable angina
• Pharmacokinetics: oral administration, slow onset of action, high protein binding, 95% cross placental barrier
• Side effects: bleeding, allergic reactions, GI disturbances, skin necrosis
• Excessive anti-coagulant effect and bleeding can be reversed by administering Vit K
• Lab control of treatment: INR (2 - 3)
• Antidote: phytomenadione
• Drug interactions: NSAIDs like aspirin displace acenocoumarol from plasma protein binding sites and enhance their plasma levels

Direct Thrombin (Factor IIa) Inhibitors and Direct Factor Xa Inhibitors

• Mechanism of action: directly bind to thrombin or factor Xa, inhibiting their actions
• Pharmacodynamics: prevention of venous thromboembolism, prevention of stroke and systemic embolism in patients with atrial fibrillation
• Pharmacokinetics: oral administration, rapid onset of action, low risk of interactions with drugs and foods, predictable pharmacokinetics and anti-coagulant effect
• Side effects: bleeding, GI disturbances may occur